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Novel Approaches for Enhancing Cell Survival and Function In Vivo
FDA has approved several cell-based therapeutics and hundreds of cell therapy clinical trials are ongoing. Cells will be a significant type of medicine after small molecule and protein drugs. However, several obstacles need to be addressed to achieve the widespread use of cellular therapeutics. The first challenge is the low efficacy of cell transplantation due to low retention, survival, integration, and function of cells in vivo. The second challenge is producing a massive number of cells for clinical treatment with cost-effectively and reproducibly technologies. In this thesis, we proposed and investigated three approaches to address these challenges. To begin with, we used two novel biomaterials to deliver cells to enhance their in vivo retention and function. The first biomaterial is a recombinant fibrin matrix which significantly improved cell delivery efficiency and safety. The second biomaterial is a novel γγ’F1:pFN complex fibrin matrix, which enhanced cell culture and improved wound healing. Moreover, injectable, microscale, 3D tissues were used to address the challenges. Brown adipose microtissues were prepared to alleviate obesity and its associated type 2 diabetes mellitus (T2DM). In addition, a novel, scalable and cell-friendly technology (AlgTubes) anchored with RGD for microtissue manufacturing was developed. Animal cells were used for preliminary study and can be used for food science to produce cultured meat. This technology has the potential to produce any cell therapy-related cell types in the future. Finally, we also systematically proposed engineering a physiologically relevant microenvironment for large-scale therapeutic cell and microtissue production.
Wang, Ou, "Novel Approaches for Enhancing Cell Survival and Function In Vivo" (2021). ETD collection for University of Nebraska - Lincoln. AAI28865393.